The major objective of the proposed research is to evaluate the carcinogenic potential and mechanism of congeners of polychlorinated biphenyls (PCBs). Tumor induction will be evaluated by long term exposure of rats, with or without partial hepatectomy, to diets containing mixtures or single PCBs (Aroclor 1260, Aroclor 1016, 2,5,2',5'-tetrachlorobiphenyl, 2,4,5,2',4',5'-pentachlorobiphenyl, 2,4,5,2',4',5'-hexachlorobiphenyl, or 2,3,6,2',3',6'-hexachlorobiphenyl). The ultrastructural changes leading to a malignant neoplasm induced by the PCBs will be sequentially evaluated. The ability of PCBs to cause malignant transformation of cell cultures will be evaluated by exposing cultures of an embryonic fibroblast cell line or of primary liver cells to mixtures, single or metabolites of the PCBs. The growth pattern leading to transformation with respect to dose will be established. Transformed cells will be injected into a susceptible host for the evaluation of tumor formation. The rates and routes of excretion of the individual PCB congeners listed above in the rhesus monkey will be evaluated. The metabolic processes of hydroxylation, dechlorination and arene oxide formation will be evaluated utilizing thin layer, high pressure liquid and gas liquid chromatography and mass nuclear magnetic resonance and infrared spectroscopy.